Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Cureus. 2024 Oct 3;16(10):e70789. doi: 10.7759/cureus.70789. eCollection 2024 
Oct.

Compact Arterial Monitoring Device Use in Resuscitative Endovascular Balloon 
Occlusion of the Aorta (REBOA): A Simple Validation Study in Swine.

Lussier G(1), Evans AJ(2), Houston I(1), Wilsnack A(2), Russo CM(2), Vietor 
R(3)(2), Bedocs P(3).

Author information:
(1)Department of Medicine, Uniformed Services University of the Health Sciences, 
Bethesda, USA.
(2)Department of Anesthesiology, Walter Reed National Military Medical Center, 
Bethesda, USA.
(3)Department of Anesthesiology, Uniformed Services University of the Health 
Sciences, Bethesda, USA.

Introduction Hemorrhage is the leading cause of preventable death in trauma in 
both the military and civilian settings worldwide. Medical studies from 
Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) informed 
change in military prehospital medicine by influencing widespread tourniquet 
distribution and training on their use to stop life-threatening extremity 
hemorrhage. In the military setting, there has been a significant reduction in 
preventable death due to extremity exsanguination since the widespread 
implementation of tourniquets within the Department of Defense. However, 
noncompressible hemorrhage remains a significant cause of mortality, especially 
in the prehospital setting. In select patients, resuscitative endovascular 
balloon occlusion of the aorta (REBOA) is an adjunct that can be utilized to 
slow or stop non-compressible hemorrhage until the patient reaches definitive 
care. However, frontline medical providers face the challenge of reliable, 
accurate blood pressure measurement in REBOA patients. REBOA, used in 
conjunction with a small disposable pressure monitor, can bridge the gap in 
capabilities, creating a more balanced resuscitation and reducing blood product 
requirements with the added benefit of invasive blood pressure monitoring 
capability. The authors of this study propose the sustained use and further 
validation of a small, disposable pressure monitor in REBOA to monitor 
beat-to-beat variation in both hemodynamically stable and unstable patients and 
seek to offer a pathway for use in austere environments. Materials and methods 
Yorkshire swine (n = 4) were selected for partial REBOA (pREBOA) placement and 
compass transducer measurement in conjunction with a vascular experimental 
protocol. Appropriate vascular and arterial line access was obtained, 
hemorrhagic shock was initiated, and REBOA with an in-line Compass™ device (CD) 
pressure transducer (Centurion Medical Products, Williamston, MI) was used to 
occlude the aorta. Mean arterial pressures were measured via the CD, recorded, 
and compared to the control arterial line at hypotensive, normotensive, and 
hypertensive pressures. Results At hypotensive pressures, 30% of the CD readings 
fell within 1 mmHg of control arterial line readings, and 52.3% were within 2 
mmHg. At normotensive pressures, 46% of the CD readings fell within 1 mmHg of 
control arterial line readings, and 64.2% were within 2 mmHg. At hypertensive 
pressures, 60% of the CD readings fell within 1 mmHg of control arterial line 
readings, and 82% were within 2 mmHg. All CD data points at all pressures were 
within 8 mmHg of the control arterial line readings. Conclusions In conclusion, 
the CD is a compact, inexpensive, portable pressure-sensing device that may 
potentially augment the safety and functionality of the REBOA in trauma patients 
both at the point of injury and in the hospital. This novel study conducted on 
four swine subjects demonstrated a remarkable correlation to the traditional 
equipment intensive arterial line setups, and issues of stasis and 
non-pulsatility were easily troubleshot. Future studies should investigate CD 
use in REBOA catheters under different physiological conditions, specifically 
arrhythmias, and in different environments (prehospital, air medical transport, 
and austere locations).

Copyright © 2024, Lussier et al.

DOI: 10.7759/cureus.70789
PMCID: PMC11531354
PMID: 39493181

Conflict of interest statement: Human subjects: All authors have confirmed that 
this study did not involve human participants or tissue. Animal subjects: 
Institutional Animal Care and Use Committee (IACUC): The research protocol was 
approved by the IACUC of the Uniformed Services University of the Health 
Sciences. Ethical approval and Trial Registration Details Per Reviewer Request 
Below: 
--------------------------------------------------------------------------------- 
USUHS / DOD – SPONSORED ANIMAL RESEARCH PROPOSALS MUST USE THIS STANDARDIZED 
FORMAT Reference DOD Directive 3216.1 & USUHS Instruction 3203 
*************************************************************************************Specific 
information requested in the following animal-use protocol template is a result 
of requirements of the Animal Welfare Act regulations (AWAR), the Guide for the 
Care and Use of Laboratory Animals, and other applicable Federal regulations and 
DOD directives. 
************************************************************************************* 
This document is intended to be an aid in the preparation of a USUHS DOD – 
sponsored animal use proposal. The instructions and written explanations 
provided for individual paragraphs (ref. animal-use protocol template in AR 
40-33 / USUHSINST 3203, Appendix C) are coded as hidden text. To see the 
instructions and examples for each section, select the “Show/Hide ¶” button on 
your tool bar. To print the hidden text, select “Print” on the drop down file 
menu. Under the “Options” button, select “Hidden text” under the “Include with 
document” section. Use of a word processor makes completion of this template a 
“fill-in-the-blanks” exercise. Please provide all response entries in the 
following font: Arial, Regular, 12, Black. Please do NOT submit this page of 
instructions with your animal protocol submission. With the exception of title 
headings, each paragraph and subparagraph in the following template must have a 
response. Portions of the template that are not applicable to your particular 
protocol, (i.e., no surgery or no prolonged restraint) should be marked “N/A”. 
There are no space limitations for the responses. Do not delete any sections. 
Pertinent standing operating procedures or similar documents that are readily 
available to your IACUC may be referenced to assist in the description of 
specific procedures. It is critical that only animal studies or procedures 
documented in an IACUC – approved protocol be performed at your facility. 
Additionally, Principal Investigators, or other delegated research personnel, 
should keep accurate experimental records and be able to provide an audit trail 
of animal expenditures and use that correlates to their approved protocol. USUHS 
FORM 3206 ANIMAL STUDY PROPOSAL PROTOCOL COVER SHEET PROTOCOL NUMBER: SUR-19-965 
PROTOCOL TITLE: Partial resuscitative endovascular balloon occlusion of the 
aorta (PREBOA) characterization of targeted distal flow and permissive regional 
hypoperfusion in a porcine model (Sus scrofa domesticus) of hemorrhagic shock 
GRANT TITLE (if different from above): NA USUHS PROJECT NUMBER// DAI GRANT 
NUMBER: Pending FUNDING AGENCY: USU USUHS Form 3206 – Revised February 2018 
Previous versions are obsolete EARLIEST ANTICIPATED FUNDING START DATE: Pending 
PRINCIPAL INVESTIGATOR: Joseph White, MAJ, MC, USA Surgery 301-319-2852 28 Feb 
2017 MAJ Joseph White, MD Department Office telephone Date SCIENTIFIC REVIEW: 
This animal use proposal received an appropriate peer scientific review and is 
consistent with good scientific research practice. CAPT Eric A. Elster 
Department Office telephone Date STATISTICAL REVIEW: A person knowledgeable in 
biostatistics reviewed this proposal to ensure that the number of animals used 
is appropriate to obtain sufficient data and/or is not excessive, and the 
statistical design is appropriate for the intent of the study. Statistics USUS 
301-295-9468 28 Feb 2017 Cara Olsen, MS, DrPH Department Office telephone Date 
ATTENDING VETERINARIAN: In accordance with the Animal Welfare Regulations, the 
Attending Veterinarian was consulted in the planning of procedures and 
manipulations that may cause more than slight or momentary pain or distress, 
even if relieved by anesthetics or analgesics. All signatures are required prior 
to submission to the IACUC Office. LAM 301-295-9492 Anna B. Mullins, DVM, DACLAM 
Department Office telephone Date BIOSAFETY OFFICER: Only required if using any 
infectious pathogens. EHS Peter Bouma Department Office telephone Date USUHS 
Form 3206 – Revised February 2018 Previous versions are obsolete ANIMAL PROTOCOL 
NUMBER: Pending PRINCIPAL INVESTIGATOR Joseph M. White, MD, FACS MAJ, MC, USA 
Assistant Program Director, Vascular Surgery Fellowship Assistant Professor of 
Surgery The Department of Surgery at Uniformed Services University of the Health 
Sciences and Walter Reed National Military Medical Center Office: 301-319-2852 
Email: joseph.m.white70.mil@mail.mil ANIMAL PROTOCOL TITLE: Partial 
resuscitative endovascular balloon occlusion of the aorta (PREBOA) 
characterization of targeted distal flow and permissive regional hypoperfusion 
in a porcine model (Sus scrofa domesticus) of hemorrhagic shock GRANT TITLE (if 
different from above): NA USUHS PROJECT NUMBER// DAI GRANT NUMBER: Pending 
CO-INVESTIGATOR(S): Todd E. Rasmussen, MD FACS Colonel USAF MC Shumacker 
Professor of Surgery Associate Dean for Clinical Research F. Edward Hebert 
School of Medicine - "America's Medical School" Uniformed Services University of 
the Health Sciences 4301 Jones Bridge Road Bethesda, Maryland 20814-4712 Office: 
301-295-3016 Mobile: 210-508-7062 Email: todd.rasmussen@usuhs.edu Paul W. White, 
MD, FACS LTC, MC, USA Program Director, Vascular Surgery Fellowship Associate 
Professor of Surgery, The Department of Surgery at Uniformed Services University 
of the Health Sciences and Walter Reed National Military Medical Center Office: 
301-295-4779 Email: paul.w.white4.mil@mail.mil Thomas A. Davis, PhD Deputy Vice 
Chair of Research Professor USUHS Form 3206 – Revised February 2018 Previous 
versions are obsolete USU Walter Reed Surgery Uniformed Services University of 
the Health Sciences 4301 Jones Bridge Road Bethesda, MD 20814 Office: 
301-295-9825 Mobile: 301-204-5212 Email: thomas.davis@usuhs.edu I. NON-TECHNICAL 
SYNOPSIS: During recent military conflicts, medics and surgeons treat combat 
trauma patients with critical injuries to the chest, abdomen, and pelvis areas 
where it can be nearly impossible to control bleeding to save a service member’s 
life. While the application of tourniquets helps prevent life-threatening blood 
loss from wounds to extremities (arms and legs), nothing exists for critical 
injuries to the chest, abdomen, and pelvis in combat and in emergency care 
environments. A new technology referred to as resuscitative endovascular balloon 
occlusion of the aorta (REBOA) has been used in trauma patients suffering from 
rapid blood loss as a result of injuries to their chest, abdomen, and pelvis. 
This technique involves rapidly placing a flexible catheter into the femoral 
artery in the groin, maneuvering, and placement in the aorta, and then inflation 
of an attached balloon at the tip to stop the uncontrolled bleeding. Not 
surprisingly, total blockage of blood flow to areas to various regions of the 
body for an extensive time period has resulted in some serious follow-on medical 
complications. In this proposal, we will test and evaluate the next generation 
of PREBOA (partial PREBOA) in a well-characterized non-survival swine hemorrhage 
model. We hypothesize that this new technology will permit longer utilization, 
enhance organ oxygenation to maintain tissue viability and increase patient 
survival II. BACKGROUND: II.1. Background: In the current conflicts, many 
wounded service members have survived catastrophic traumatic injuries. They 
would have died from these injuries in previous wars, but improvements in 
battlefield medical care and the use of body armor have increased survival 
rates. Hemorrhage, particularly non-compressible torso hemorrhage (NCTH), has 
been identified as a leading cause of preventable death on the modern 
battlefield.[1,2] Analysis from the recent wars in Iraq and Afghanistan has 
demonstrated that hemorrhage was the underlying physiologic insult in 90% of 
potentially survivable battlefield injuries.[3] The stratification of mortality 
from death on the battlefield from 2001-2011 (Iraq and Afghanistan) demonstrated 
that 87.3% of all injury mortality occurred in the pre-MTF environment.[3] Of 
the pre-MTF deaths, 75.7% (n = 3,040) were classified as nonsurvivable, and 
24.3% (n = 976) were deemed potentially survivable (PS). The injury/physiologic 
focus of PS acute mortality was largely associated with hemorrhage (90.9%). The 
site of lethal hemorrhage was truncal (67.3%), followed by junctional (19.2%) 
and peripheral-extremity (13.5%) hemorrhage. The management of traumatic 
hemorrhage (specifically, NCTH) requires innovative strategies and devices to 
overcome the current trend identified in modern combat. PREBOA seeks to address 
this critical gap and alter casualty mortality rates as a result. Resuscitative 
Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as a promising 
technique for cases of severe NCTH during trauma. An emerging set of 
pre-clinical and clinical data on the use of REBOA reports highly successful 
outcomes following brief periods of occlusion; however, longer periods of 
occlusion are associated with significantly increased mortality.[4,5] 
Therapeutic strategies that incorporate regulated partial distal aortic flow and 
perfusion are a potential technique to mitigate ongoing distal ischemia and 
subsequent reperfusion injury while potentially avoiding the deleterious USUHS 
Form 3206 – Revised February 2018 Previous versions are obsolete complications 
of distal clot disruption with ongoing hemorrhage and supraphysiologic central 
and cerebral pressures.[6] In order to allow distal aortic flow and perfusion at 
a controlled and regulated level, REBOA distal flow characteristics require 
additional pre-clinical testing and evaluation. The PREBOA-PRO Catheter utilizes 
the same basic technological characteristics as the existing ER-REBOA Catheter – 
complete large vessel occlusion and blood pressure monitoring – with minor 
modifications to the balloon design to help facilitate a smoother transition 
between full occlusion and no occlusion. The PREBOA-PRO Catheter employs a 
composite balloon design that arranges a non-compliant partner or “spine” 
balloon in parallel with a compliant occlusion balloon. When the balloon system 
is fully inflated, complete occlusion is achieved. During balloon deflation, 
bypass channels initially open around the partner balloon, allowing a limited 
amount of blood to flow past the balloon, while maintaining balloon wall 
apposition Figure 1). This permits modulation of blood pressure gradient across 
the balloon during inflation/deflation cycles. Partial REBOA is a a technique, 
which shows great promise to reduce morbidities associated with survival from 
REBOA and extend the amount of time in which REBOA can be performed. REBOA is a 
resuscitative adjunct that augments central and cerebral perfusion while 
mitigating lethal hemorrhage secondary to NCTH. Next generation Prytime Medical 
Devices Inc. partial REBOA (PREBOA-PRO) catheter is currently not FDA-approved 
for use. Standard REBOA catheter systems are currently in use in military Role 
I, II, and III facilities and Medical Treatment Facilities. Forward elements 
such as GHOST-T (Golden Hour Offset Surgical Treatment-Teams) and SOST (Special 
Operations Surgical Teams) have incorporated and implemented REBOA technology on 
the forward edge of the battlefield. Civilian level 1 trauma centers currently 
use REBOA catheter systems. Clinical use typically employs “all-or-nothing” 
REBOA, meaning that the balloon is fully inflated or completely deflated. PREBOA 
allows for distal aortic flow, potentially expanding the resuscitation envelope. 
This would represent lengthening the “golden hour” and augmenting austere or 
prolonged field care. Permissive Regional Hypoperfusion (PRH) following complete 
aortic occlusion incorporates regulated partial distal aortic flow and perfusion 
with subsequent mitigation of distal ischemia and reperfusion injury. This 
concept potentially avoids the deleterious complications of distal clot 
disruption with ongoing hemorrhage and supraphysiologic central and cerebral 
pressures. Building upon the knowledge acquired during previous REBOA testing: 
REBOA Distal Flow Dynamics and Targeted Distal Flow Characterization (which 
characterizes the flow-volume relationship and TDF fidelity), this project 
attempts to identify the critical flow threshold at which Permissive Regional 
Hypoperfusion (PRH) allows for optimal metabolic and physiologic results. The 
overarching goal is to decrease morbidity and mortality in the out-of-hospital 
(prehospital, en-route and far forward medicine) environment scenarios using a 
partial occlusive endovascular device (pREBOA) to lessen hypotension and 
ischemia-reperfusion injury while augmenting pulmonary and cerebral perfusion. 
In this study, we will compare several state-of the-art intravascular occlusion 
devices in a swine model of lethal non-compressible torso hemorrhage (NCTH). 
Figure 1: The pREBOA-PROTM Catheter USUHS Form 3206 – Revised February 2018 
Previous versions are obsolete II.2. Literature Search for Duplication: II.2.1. 
Literature Source(s) Searched: PubMed, DTIC, and NIH RePORT were searched to 
avoid unnecessary duplication of research. II.2.2. Date of Search: 8 January 
2018 II.2.3. Period of Search: 1990 to present II.2.4. Key Words and Search 
Strategy: Separate search terms: PREBOA (partial resuscitative endovascular 
balloon occlusion of the aorta) in a large animal model (9) REBOA (resuscitative 
endovascular balloon occlusion of the aorta) in a large animal model (14) 
Combined search terms: PREBOA (partial resuscitative endovascular balloon 
occlusion of the aorta) in a large animal model AND Sus scrofa domesticus (7) 
REBOA (resuscitative endovascular balloon occlusion of the aorta) in a large 
animal model AND Sus scrofa domesticus (9) PREBOA (partial resuscitative 
endovascular balloon occlusion of the aorta) in a large animal model AND 
Hemorrhagic shock (7) REBOA (resuscitative endovascular balloon occlusion of the 
aorta) in a large animal model AND Hemorrhagic shock (9) (Please see appendix A) 
II.2.5. Results of Search: Summary: No studies were identified in the literature 
that would appear to duplicate the proposed large-animal research project. The 
PREBOA-PRO prototype to be evaluated is novel, and no duplicative in vivo 
studies were identified. Please see Appendix A for Search Results. III. 
OBJECTIVE\HYPOTHESIS: The objectives of this study are two-fold (1) to 
characterize distal aortic flow following PREBOA using the ER-REBOA, and 
PREBOA-PRO catheters in an established, translational, swine model of lethal 
NCTH and (2) to identify the critical threshold at which Permissive Regional 
Hypoperfusion (PRH) allows for reduced perfusion pressure promoting clot 
stabilization (avoidance of hemorrhage), mitigates tissue ischemia and 
reperfusion injury, and dampens supraphysiologic central and cerebral pressures. 
We hypothesis the PREBOA-PRO catheters will demonstrate superior Targeted Distal 
Flow (TDF) fidelity compared to the ER-REBOA and that a TDF of 150mL/min will 
demonstrate. USUHS Form 3206 – Revised February 2018 Previous versions are 
obsolete clot stabilization (avoid free intraperitoneal hemorrhage), mitigate 
distal ischemia and reperfusion injury and result in a reduction of 
supraphysiologic central and cerebral pressures thereby demonstrating superior 
Permissive Regional Hypoperfusion (PRH). IV. MILITARY RELEVANCE: Eastridge and 
colleagues reported that hemorrhage is the leading cause of preventable death on 
the modern battlefield. Between October 2001 and June 2011, 4,596 battlefield 
fatalities were reviewed and analyzed during the wars in Iraq and Afghanistan. 
The stratification of mortality demonstrated that 87.3% of all injury mortality 
occurred in the pre-MTF (Medical Treatment Facility) environment. Of the pre-MTF 
deaths, 75.7% (n = 3,040) were classified as nonsurvivable, and 24.3% (n = 976) 
were deemed potentially survivable (PS). The injury/physiologic focus of PS 
acute mortality was largely associated with hemorrhage (90.9%). The site of 
lethal hemorrhage was truncal (67.3%), followed by junctional (19.2%) and 
peripheral-extremity (13.5%) hemorrhage.[3] The management of hemorrhage is 
critical to improving combat causality care (CCC) in the military. Resuscitative 
Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as a promising 
technique for cases of severe NCTH during trauma. Prompt control of bleeding and 
resuscitation in the field can reduce mortality by as much as 20%. Importantly, 
hemorrhage is a major mechanism of death in potentially survivable combat 
injuries, underscoring the necessity for initiatives to mitigate bleeding and to 
develop new solutions to provide for prolonged Damage Control Resuscitation 
(pDCR), particularly in the prehospital-en route and prolonged field care (PFC) 
austere environment. Treatments initiated within the “Golden Hour”- 60 minutes 
post-injury have resulted in increased survival. REBOA devices provide a 
short-term survival advantage by preventing exsanguination and augmenting 
perfusion of the heart, lungs, and brain. However, experimental observation 
suggests that complete aortic occlusion using REBOA can lead to severe 
multifactorial complications, including myocardial dysfunction, respiratory 
distress, traumatic brain injury, and distal organ/extremity 
ischemia-reperfusion injury, resulting in multi-organ dysfunction and death. 
Therapeutic strategies that incorporate regulated partial distal aortic flow and 
perfusion are a potential technique to mitigate ongoing distal ischemia and 
subsequent reperfusion injury while potentially avoiding the deleterious 
complications of distal clot disruption with ongoing hemorrhage and 
supraphysiologic central and cerebral pressures. In order to allow distal aortic 
flow and perfusion at a controlled and regulated level, REBOA distal flow 
characteristics require additional investigation. V. MATERIALS AND METHODS: V.1. 
Experimental Design and General Procedures: General Overview/Concept Specific 
Aims Model Development Animals: Two animals from each experimental group will be 
considered a pilot study for each named study. These animals will be used to 
teach and perfect various aspects procedures associated with two proposed animal 
models (Section V.4.3.2. Procedure) to include but not limited to the surgical 
preparation, sedation, intubation, anesthesia monitoring, cut downs, placement 
of arterial and venous lines, injury induction, REBOA insertion and placement, 
radiographic assessments, as well clinical and laboratory monitoring. USUHS Form 
3206 – Revised February 2018 Previous versions are obsolete Experiment 1: In a 
controlled prefixed bleed hemorrhagic shock model, evaluate and characterize 
distal aortic flow rate capabilities with the ER-REBOA, PREBOA-PRO (N=2 pilot 
animals + 8 animals per treatment arm; total 18 animals). Experiment 2: 
Following complete aortic occlusion and PRH in a swine traumatic liver 
amputation uncontrolled bleed hemorrhagic shock model (approximately 30% of the 
liver followed by 1.5 minutes of free hemorrhage), evaluate and characterize 
associated hemodynamics and metabolic/physiologic consequences of TDF at 50 
mL/min (Grp 1), 150 mL/min (Grp 2), 300 mL/min (Grp 3), 500 mL/min (Grp 4) and 
1000 mL/min (Grp 5). N=2 pilot animals + 8 animals per treatment arm; total 42 
swine. (*Please see section V.4.3.2. Procedure for additional operative details 
regarding the specific sequence of events/conduct of the operation) V.1.1. 
Experiment 1: Target Distal Perfusion (18 animals) (USDA pain category D) 
Experimental Design 1: Uncontrolled bleed hemorrhagic shock (HS) will be 
simulated by withdrawing 25% of estimated blood volume through an arterial 
sheath into citrated blood collection bags over a 30-minute period to simulate 
the prehospital environment. Complete aortic occlusion will be initiated by 
inflating the aortic occlusion balloon catheter until there is loss of a distal 
arterial waveform and occlusion will be sustained for 20 minutes. After 15 
minutes of occlusion, shed blood volume will be returned through the central 
venous line via rapid infusion (Belmont Instruments, Billerica, MD) at the rate 
of 150 cc/min. Following 20 minutes of Zone I aortic occlusion, incremental 
balloon deflation at a rate of 0.5 cc every 30 seconds will occur until the 
balloon is completely deflated. Physiologic parameters and aortic flow 
measurements will be collected. Onset of aortic flow during balloon deflation 
will be defined as the time point when flow reaches 50 mL/min (approximately 2% 
of baseline full flow) to account for the fidelity of the aortic flow probe at 
very low flow rates. The estimated time for incremental balloon deflation is 
15-20 minutes (average balloon total volume: 5.25cc-7.25cc). Upon completion of 
the incremental balloon deflation, the subsequent phase of testing will 
determine balloon fidelity and the ability to provide a targeted distal flow. 
Using data extracted from the initial phase of the experiment, a balloon volume 
that corresponds with a targeted distal flow of 150ml/min will be selected. The 
aortic occlusion balloon catheter will be inflated and targeted distal flow 
recorded over a 90 minute period. At the end of the experiment, the animals will 
be humanely euthanized according to V.4.6. V.1.2. Experiment 2: Permissive 
Regional Hypoperfusion (42 animals) (USDA pain category D) Experimental Design 
2: HS shock will be initiated by traumatic amputation of the liver 
(approximately 30% total liver volume) followed by 1.5 minutes of free 
hemorrhage. The liver will be marked along the planned transection plane, 2 cm 
to the left of Cantlie's line, to provide amputation of approximately 80% of the 
left lateral lobe of the liver and 40% of the left medial lobe of the liver 
(approximately 30% of total liver volume) similar to previous descriptions. At 
Time 0, the liver will be sharply transected, and the abdomen rapidly closed 
with cable ties. Complete occlusion of the aorta will be achieved with REBOA 1.5 
minutes following the initiation of injury. Complete aortic occlusion will be 
initiated by inflating the PREBOA-Pro until there is loss of a distal arterial 
waveform and occlusion is sustained for 20 minutes. Following 20 minutes of Zone 
I aortic occlusion, PRH with partial aortic occlusion will occur. The pREBOA 
will be deflated to achieve a distal aortic flow of 50mL/min (Group 1), 
150mL/min (Group 2), USUHS Form 3206 – Revised February 2018 Previous versions 
are obsolete 300mL/min (Group 3), 500mL/min (Group 4) and 1000 mL/min (Group 5). 
The variable deflation of occlusion balloon will correlate to the goal TDF 
specific to Groups 1-5. PRH phase will continue for 70 minutes. Next, study 
animals will undergo a damage control surgery with definitive hemorrhage control 
and resuscitation with whole blood. Blood volume will be returned through the 
central venous line via rapid infusion (Belmont Instruments, Billerica, MD) at 
the rate of 150 cc/min. The REBOA catheter will be removed and the study animals 
will complete a 240- minute critical care phase (continued hemodynamic 
monitoring and resuscitation). At the end of the experiment, the animals will be 
humanely euthanized according to V.4.6. 2 Animals are for pilot. V.2. Data 
Analysis: Experiment 1: Two endovascular balloon occlusion devices (ER-REBOA and 
PREBOA-PRO) will be tested and evaluated. The association between flow and 
volume will be assessed for each experimental animal using linear regression 
with flow as the dependent variable and volume as the independent variable. For 
overall comparisons, the separate regressions will be combined across animals 
and compared between groups using a multilevel regression model with 
subject-specific random intercepts and slopes, and fixed effects of group, 
volume, and the interaction of group and volume. A primary hypothesis is that 
the slope (the increase in flow corresponding to a specific decrease in volume) 
will be greater in the ER-REBOA group than in the PREBOA-PRO (next generation 
REBOA catheter) group. With a sample size of 8 animals per group and an average 
of 15 measurements per animal, if the within-animal correlation is 0.5, the 
study will have 80% power to detect a significant difference if, across the 
range of volumes, the increase in flow is lower in the PREBOA-PRO group than the 
ER-REBOA group by 0.74 standard deviations. If the standard deviation of the 
distal flow rate is close to 300 mL/minute, as has been observed in similar 
studies, this corresponds to a result in which the difference in flow rates from 
the lowest to the highest volume is reduced in the PREBOA-PRO group by 222 
mL/minute compared to the ER-REBOA group. For testing whether the variability in 
flow level over time differs between groups, the within- subject standard 
deviation will be calculated for each animal and these standard deviations will 
be compared between groups using a Mann-Whitney U test. Although we have no 
prior data on the within-subject standard deviation, the power of the 
Mann-Whitney U test is expected to be similar to that of a corresponding 
Student's t test. With 8 animals per group, the study will have 80% power to 
detect a difference of 1.5 standard deviations. Actual power may be slightly 
lower but is still expected to be adequate. Experiment 2: Five distal flow rates 
will be evaluated in order to determine optimal regional permissive hypotension 
following partial REBOA in a model of lethal hemorrhagic shock. Mortality will 
be compared across groups using Fisher's exact test. When comparing the flow 
rate with the highest vs. lowest mortality rate, if mortality is 90% vs. 10% and 
the sample size is 8 per group, Fisher's exact test with a 5% two-sided 
significance level will have 80% power to detect a difference. If a Bonferroni 
adjustment is used to account for pairwise comparisons among 5 groups (flow 
rates) the power will be 80% to detect a significant difference if the true 
rates are 95% and 5%. Therefore, the sample size is sufficient to detect the 
expected large differences in mortality. Histologic, physiologic and metabolic 
parameters will be compared across groups using one- way ANOVA followed by 
Tukey's pairwise comparisons. A sample size of 8 per group will have 80% power 
to detect differences of 1.9 standard deviations between groups based on ANOVA 
contrasts with 5% two-sided significance level after adjustment for multiple 
comparisons. USUHS Form 3206 – Revised February 2018 Previous versions are 
obsolete V.3. Laboratory Animals Required and Justification: V.3.1. Non-animal 
Alternatives Considered: No feasible non-animal alternatives are available to 
study PREBOA physiology with metabolic and physiologic endpoints. V.3.2. Animal 
Model and Species Justification: Swine species allows for significant advantage 
due to the animals arterial capacity (i.e. arterial size and structural 
similarity to human arteries) to allow for and facilitate most endovascular 
devices and procedures. Specifically, the porcine common femoral artery can 
accommodate 7 French arterial sheaths (the required arterial sheath size for the 
PREBOA-PRO and ER- REBOA-PRO catheter). Additionally, histologic similarities 
between swine and human aneurysmal models are favorable. V.3.3. Laboratory 
Animals ALTERNATIVES CONSIDERATIONS: Does the protocol have any provisions that 
would qualify it to be identified as one that Refines, Reduces, or Replaces 
(3R's) the use of animals in relation to other protocols or procedures performed 
in the past? Y/N (circle): YES SECTION V.3.5. Exceptions to the Guide for the 
Care and Use of Laboratory Animals (Please check all applicable): Use of 
Paralytics (V.4.1.2.3.) Prolonged Restraint (V.4.2.) Multiple Major Survival 
Surgery (V.4.3.6.) Use of